The present invention relates generally to beacons in the Time-Reversal Acoustics (TRA) systems used to focus acoustic waves for various useful applications in the biomedical area. More particularly, the beacon of the invention provides an electromagnetic wave signal in response to received acoustic waves, which may be used as a feedback signal for tuning time-reversal acoustic system to focus acoustic waves at the location of such beacon for various useful purposes, such as charging a battery of an implant attached to the beacon. The device and method of the invention may be used advantageously as part of a medical instrument inside a patient's body as well as for other applications described below in more detail.
For the purposes of this description, the term “patient” is used to describe any person, animal, or other living being in which the medical instrument is inserted temporarily or implanted on a permanent basis. The term “medical instrument” or just “instrument” is used to describe various medical inserts and implants such as but not limited to catheters, needles, various scopes of flexible or rigid nature, implants, stents including drug-eluting stents, pacemakers and parts thereof, implantable electrical stimulators of all kinds including neurostimulators, neuromodulation devices, vagus nerve stimulators, hypoglossal nerve stimulators, thalamus stimulators, sacral nerve stimulators and spinal cord stimulators, implantable hearing aid devices including inner ear microtransmitters, cannulas, balloons, probes, guidewires, trocars, sensors, markers, infusion pumps, various implants functioning from an internal battery, and local medication delivery devices.
In medicine, the present invention may be used most advantageously with TRA methods and devices designed for various diagnostic and therapeutic ultrasound and other acoustic wave applications including ultrasonic hyperthermia and ablation of tumors, cavitational destruction of tissues, ultrasound imaging and image-guided interventions, ultrasonic lithotripsy, ultrasound-assisted drug delivery, ultrasonic surgery, and remote charging of batteries in the implanted devices. In therapeutic applications, absorbed ultrasound energy is used to change the state of a target area. In particular, ultrasound energy applied at high power densities can induce significant physiological effects on tissues. These effects may result from either thermal or mechanical response of the tissue subjected to ultrasound energy. Thermal effects include hyperthermia and ablation of tissue. The absorption of ultrasound energy at the target area induces a temperature rise, which causes coagulation or ablation of target area cells. In therapeutic applications of ultrasound, it is important that the applied ultrasound energy causes an intended change of state solely at a target area without adversely affecting other tissue within the patient. The effective therapeutic dose must be delivered to the target area while the thermal and mechanical effects in intermediary and surrounding tissue are minimized. Therefore, proper focusing and control is one of the primary criteria for successful therapeutic application of ultrasound.
Examples of the use of ultrasound in medicine can be found throughout the prior art. U.S. Pat. No. 5,590,657 to Cain et al. describes a high intensity ultrasound system including a phased array of ultrasound transducers located outside the patient. Methods for refocusing the beam are described. U.S. Pat. No. 6,128,958 to Cain describes architecture for driving an ultrasound phased array. U.S. Pat. No. 5,769,790 to Watkins et al. describes a system for combining ultrasound therapy and imaging. U.S. Pat. No. 5,762,066 to Law et al. describes a high intensity ultrasound system consisting of an intracavity probe having two active ultrasound radiating surfaces with different focal geometries. U.S. Pat. No. 5,366,490 to Edwards et al. describes a method for applying destructive energy to a target tissue using a catheter. U.S. Pat. Nos. 5,207,214 and 5,613,940 to Romano describe an array of reciprocal transducers which are intended to focus intense sound energy without causing extraneous tissue damage. Finally, U.S. Pat. No. 5,241,962 to Iwama describes the use of ultrasonic pulses and echo signals to disintegrate a calculus.
Focusing of ultrasonic waves is a fundamental aspect of the most of the medical applications of ultrasound. The efficiency of ultrasound focusing in biological tissues is often significantly limited by spatial heterogeneities in sound velocity in tissues and the presence of various reflective surfaces and boundaries. The refraction, reflection and scattering of ultrasound in inhomogeneous media can greatly distort focused ultrasound field. There are many methods for improving the ultrasonic focusing in complex media based on the phase and amplitude corrections in focusing system but they are often too complicated and in some cases do not provide necessary improvement. The concept of TRA developed initially by M. Fink of the University of Paris provides an elegant possibility of both temporal and spatial concentrating of acoustic energy in highly inhomogeneous media. The TRA technique is based on the reciprocity of acoustic propagation, which implies that the time-reversed version of an incident pressure field naturally refocuses on its source. The general concept of TRA is described in an article by Fink, entitled “Time-reversed acoustics,” Scientific American, November 1999, pp. 91-97, which is incorporated herein by reference. U.S. Pat. No. 5,092,336 to Fink, which is also incorporated herein by reference, describes a device for localization and focusing of acoustic waves in tissues.
An important issue in the TRA method of focusing acoustic energy is related to obtaining initial signal from the in the target area. It is necessary to have some sort of beacon to provide an initial signal from the focal region. In the TRA systems described in the prior art, most common beacon is a hydrophone placed at the chosen target point. Other possible beacons are highly reflective targets that provide an acoustical feedback signal for TRA focusing of acoustic beam. This requirement of having a beacon in the target region limits the applications of TRA focusing methods.
U.S. Pat. No. 6,161,434 to Fink et al., which is incorporated herein by reference, describes methods to use time-reversed acoustics to search for a faint sound source. U.S. Pat. No. 5,428,999 to Fink, which is also incorporated herein by reference, describes methods for detecting and locating reflecting targets, ultrasound echographic imaging, and concentrating acoustic energy on a target.
Remarkably, scattering and numerous reflections from boundaries, which may greatly limit and even completely diminish conventional focusing, lead to the improvement of the focusing ability of the TRA system. Fink et al. have demonstrated a remarkable robustness of TRA focusing: the more complex the medium, the sharper the focus.
The advantages of the TRA-based focusing systems (TRA FS) over conventional ultrasound focusing are as follows:    1. TRA FS is capable to precisely deliver ultrasound energy to the chosen region regardless of the heterogeneity of the propagation medium, for example behind the ribs or inside the skull. The ability to effectively localize ultrasound energy and avoid exposure of surrounding tissues is important in many medical applications including ultrasound surgery and the ultrasound enhanced drug delivery.    2. TRA FS can produce more effective spatial concentration of ultrasound energy than traditional systems; the focus volume can approach ultrasound diffraction limit, it can be spherical rather than elongated ellipsoidal typically formed by most traditional focusing systems.    3. TRA FS can produce pulses with arbitrary waveforms in a wide frequency band. Ability to generate various waveforms is important in many applications, for example for optimizing the outcome of the ultrasound stimulated drug delivery where the main mechanism of ultrasound action, sonoporation, is related to cavitation and the threshold of cavitation depends strongly on frequency and the form of the applied signal.
Several examples of TRA FS employing a passive ultrasound reflector or an active ultrasound emitter as a TRA beacon are described in the U.S. patent application Ser. No. 10/370,134 (US Patent Application Publication No. 2004/0162550) and U.S. patent application Ser. No. 10/370,381 (US Patent Application Publication No. 2004/0162507) to Govari et al. as well as a European Patent Application No. EP1449564, all of which are incorporated herein by reference. Described here is a TRA-based high intensity ultrasound system designed for isolation of pulmonary veins. The beacons, described in these references, are an active or passive piesotransducers designed to reflect or emit ultrasound signal to be detected by an array of transducers. In case of an active beacon, the electrical energy is typically delivered thereto via electrical leads from the control unit. The electrical energy is converted by the active beacon into the acoustic energy and transmitted to the outside the body where it is picked up by outside sensors to determine the exact location of the beacon. In some other cases, wireless circuitry and method of energy transmission is used to transmit the electrical energy to the active beacon, which is then again is converted to the acoustic energy emanated by the beacon. Alternatively, the beacon may comprise a passive ultrasound reflector, such as the one having a geometry that produces a sharp and easily distinguishable ultrasound signature. Alternative designs of the reflector include the design with substantially higher reflectivity of the ultrasound signal then that of the surrounding tissues, including the design of the beacon with predefined resonant frequency and high Q or a bubble containing an ultrasound agent.
Another important area of medical application of ultrasound is selective drug delivery, specifically for cancer treatment. Tumor chemotherapy is often associated with severe side effects caused by the interactions of cytotoxic drugs with healthy tissues. In addition, tumor cells often develop resistance to drugs in the course of chemotherapy (cross-resistance or multi-drug resistance). Direct injection of drugs in the tumor substantially reduces or eliminates side effects of chemotherapy and increases therapeutic windows of drugs.
Acoustically activated drug delivery systems are typically therapeutic agents bound to nano- or micro-scale carriers. These are administered to a patient and then activated by extracorporeal ultrasound transducers. Acoustic activation releases the therapeutic agent and induces cavitation that enhances drug uptake in the patient's cells. A high dosage of toxic drugs may be delivered to a point of interest while minimizing negative side effects.
Acoustic activation technology shows promise for the treatment of drug-resistant cancer tumors, vascular disease, and other diseases. Triggering the intracellular drug uptake by focused ultrasound enhances treatment efficacy. Ultrasound is proven to be an effective drug delivery modality. An advantage of ultrasound in this application is that it is non-invasive, can penetrate deep in the interior of the body, and can be carefully controlled via a number of parameters including frequency, power density, duty cycles, and time of application. Gene therapy researchers have reported recently a ten-fold increase in DNA uptake. In-vitro experiments suggest that acoustic activation therapy may be effective in treating multidrug-resistant tumors, which are very resistant to conventional treatments. Physicians do not currently have a means to accurately sonicate only an area of interest where the drug has been injected, in order to improve drug uptake to diseased cells and reduce side effects to healthy tissue.
Non-invasive recharging of implant batteries emerges as a very important area of need for great many medical devices of today. According to the article published in Business Week on Mar. 7, 2005 on pages 74-82 by Michael Arndt and entitled “Rewiring the Body”, new electrical stimulation and neurostimulation devices hold great promise to treat a variety of diseases including depression, paralysis, migraines, sleep apnea, angina, obesity, digestive tract disorders, Alzheimer's, obsessive-compulsive disorder, Parkinson's, epilepsy and many others. Already today, as many as 190,000 patients in the US are wearing electrodes in their heads to control tremors associated with Parkinson's disease and 60,000 patients have an inner ear implant to improve hearing. Advances in nerve stimulation hold tremendous promise of relief to millions of patients worldwide. There are for example up to 3 million Americans suffering with chronic migraines and about 4 million Americans who are morbidly obese. Neurostimulators hold great promise for these patients.
However, the infection risk of implantation procedure is not trivial. For cardiac pacemakers, this risk is as high as 3 to 4 percent, which is twice the infection risk of the surgery in general. Present day devices contain an internal battery, which can last as long as 5-10 years, after which time the device should be replaced with another surgery. To reduce the infection risk associated with a second implant, the need exists for a device allowing internal recharging of an existing implant battery in a non-invasive manner. Acoustic energy can be transmitted to the site of an implant. The need exists for a device allowing high-intensity energy to be directed at the exact location of an implant and then transforming that energy into electrical energy usable to recharge the implant battery. Another need exists for an internal device capable of receiving high-intensity acoustic energy and converting it to electrical power to drive various additional implant devices associated with electrical stimulators.
The need also exists in general for a system capable of more accurately focusing of acoustic energy in the region of interest inside the body. More specifically, the need exists for a method and device for TRA focusing with remote wireless feedback from the focal point without inserting a hydrophone in the target area. The need further exists for a system allowing focusing of ultrasound energy only on an area having a desired size and shape.